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Título del libro: Cellular Endocrinology In Health And Disease, Second Edition
Título del capítulo: Intracellular Trafficking of G Protein-Coupled Receptors to the Cell Surface Plasma Membrane in Health and Disease

Autores UNAM:
ALFREDO ANTONIO ULLOA Y AGUIRRE; TERESA DE JESUS ZARIÑAN GARCIA;
Autores externos:

Idioma:

Año de publicación:
2021
Palabras clave:

Conformational diseases; G protein-coupled receptors; GPCR; Intracellular trafficking; Misfolding; Misrouting; Pharmacoperones; Quality control system


Resumen:

Proteins are synthesized in the endoplasmic reticulum (ER) of the cell, where a strict quality control system (QCS) guards against aberrant protein structures and non-productive protein aggregation. The ER QCS checks for adequate folding and structural integrity of nascent proteins so that only properly folded and assembled secretory and membrane proteins may reach their final destination within the cell. For this task, the ER QCS relies on different strategies, including the action of members of major molecular chaperone families. As any other protein, G protein-coupled receptors (GPCRs) are subjected to structural and conformational scrutiny at the ER before processing and trafficking to the plasma membrane. Mutations in these integral membrane proteins may provoke misfolding, retention, and eventually degradation of the defective protein receptor, leading to disease. In this chapter, we review the mechanisms governing upward and downward trafficking of this class of membrane receptors, including interactions with molecular chaperones and scaffold molecules, and the role of some structural requirements for proper intracellular trafficking. We also exemplify how misfolding may lead to disease and describe different strategies to rescue the function of misfolded GPCRs in vitro and in vivo. © 2021 Elsevier Inc. All rights reserved.


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